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Date Printed: December 16, 2017: 09:27 PM

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This medical policy (medical coverage guideline) is Copyright 2017, Blue Cross and Blue Shield of Florida (BCBSF). All Rights Reserved. You may not copy or use this document or disclose its contents without the express written permission of BCBSF. The medical codes referenced in this document may be proprietary and owned by others. BCBSF makes no claim of ownership of such codes. Our use of such codes in this document is for explanation and guidance and should not be construed as a license for their use by you. Before utilizing the codes, please be sure that to the extent required, you have secured any appropriate licenses for such use. Current Procedural Terminology (CPT) is copyright 2017 American Medical Association. All Rights Reserved. No fee schedules, basic units, relative values, or related listings are included in CPT. The AMA assumes no liability for the data contained herein. Applicable FARS/DFARS restrictions apply to government use. CPT® is a trademark of the American Medical Association. The use of specific product names is illustrative only. It is not intended to be a recommendation of one product over another, and is not intended to represent a complete listing of all products available.

09-J2000-83

Original Effective Date: 09/15/17

Reviewed: 08/09/17

Revised: 00/00/00

Next Review: 03/14/18

Subject: Neratinib (Nerlynx)

THIS MEDICAL COVERAGE GUIDELINE IS NOT AN AUTHORIZATION, CERTIFICATION, EXPLANATION OF BENEFITS, OR A GUARANTEE OF PAYMENT, NOR DOES IT SUBSTITUTE FOR OR CONSTITUTE MEDICAL ADVICE. ALL MEDICAL DECISIONS ARE SOLELY THE RESPONSIBILITY OF THE PATIENT AND PHYSICIAN. BENEFITS ARE DETERMINED BY THE GROUP CONTRACT, MEMBER BENEFIT BOOKLET, AND/OR INDIVIDUAL SUBSCRIBER CERTIFICATE IN EFFECT AT THE TIME SERVICES WERE RENDERED. THIS MEDICAL COVERAGE GUIDELINE APPLIES TO ALL LINES OF BUSINESS UNLESS OTHERWISE NOTED IN THE PROGRAM EXCEPTIONS SECTION.

           
Dosage/ Administration Position Statement Billing/Coding Reimbursement Program Exceptions Definitions
           
Related Guidelines Other References Updates    
           

DESCRIPTION:

Approximately 255,000 new cases of breast cancer are predicted to be diagnosed in the United States in 2017. It is estimated that 20 to 50% of those diagnosed with early stage breast cancer will eventually progress to metastatic breast cancer.

Neratinib (Nerlynx), a kinase inhibitor that irreversibly binds to epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2 (HER2), and HER4, was approved by the U.S. Food and Drug Administration (FDA) in July 2017 for the extended adjuvant treatment of adult patients with early stage HER2-overexpressed/amplified breast cancer, to follow adjuvant trastuzumab-based therapy.

The safety and efficacy of neratinib were evaluated in women (n=2,840) with early-stage (1-3), node positive, HER2-positive breast cancer that were within two years of completing adjuvant trastuzumab in a multicenter, randomized, double-blind, placebo-controlled trial (ExteNET trial, NCT00878709). Subjects were randomized to receive either neratinib (n=1420) or placebo (n=1420) for one year. The major efficacy outcome measure was invasive disease-free survival (iDFS), defined as the time between the randomization date to the first occurrence of invasive recurrence (local/regional, ipsilateral or contralateral breast cancer), distant recurrence, or death from any cause, within two years and 28 days of follow-up.

Extended therapy with neratinib 240 mg/day for 12 months significantly reduced the risk of an invasive disease event at 2 years by 33% compared with placebo after trastuzumab-based adjuvant therapy. After two years, iDFS was 94.2% in patients treated with neratinib compared with 91.9% in those receiving placebo (HR 0.66; 95% CI: 0.49, 0.90, p=0.008). Overall survival data are immature.

Prespecified subgroup analysis showed a greater iDFS benefit to patients with hormone receptor-positive disease than those with hormone receptor-negative disease. The majority of patients were 50 years or older (60%) and postmenopausal (53%) with node-positive (76%) and hormone receptor-positive (57%) disease. The duration of adjuvant trastuzumab therapy was 11.5 months, with 38% of patients receiving sequential trastuzumab plus chemotherapy (previous neoadjuvant or adjuvant anthracycline plus taxane, 68%) versus concurrent therapy. Median duration of time since last dose of trastuzumab was 4.5 months.

Diarrhea was the most common Grade 3 adverse event (neratinib, 40% vs placebo, 2%). Cardiac toxicity was minimal, with Grade 2 or greater decreases in left ventricular ejection fraction occurring in 1% of patients in each group. Patients who received neratinib in this trial were not required to receive any prophylaxis with antidiarrheal agents.

National Comprehensive Cancer Network (NCCN) Guidelines for Breast Cancer (Version 2.2017) have not yet been updated to include neratinib.

POSITION STATEMENT:

Comparative Effectiveness

The FDA has deemed the drug(s) or biological product(s) in this coverage policy to be appropriate for self-administration or administration by a caregiver (i.e., not a healthcare professional). Therefore, coverage (i.e., administration) in a provider-administered setting such as an outpatient hospital, ambulatory surgical suite, physician office, or emergency facility is not considered medically necessary.

Initiation of neratinib (Nerlynx) meets the definition of medical necessity when ALL of the following criteria are met:

1. Member is diagnosed with stage 1-3 node-positive breast cancer

2. Member has HER2-positive disease as documented by ONE of the following – laboratory documentation must be provided:

a. Immunohistochemistry (IHC) is 3+

b. Fluorescent in situ hybridization (FISH) HER2 gene copy is greater than 6

c. FISH ratio of HER2 gene/chromosome 17 ratio is greater than or equal to 2.0

3. Member meets one of the following:

a. Currently receiving adjuvant trastuzumab (Herceptin)-based therapy

b. Completed adjuvant trastuzumab (Herceptin)-based therapy up to 2 years previously

4. Member has not previously been treated with OR has received less than one year of treatment with neratinib

5. Dose does not exceed 240 mg daily

Approval duration: 6 months

Continuation of neratinib (Nerlynx) meets the definition of medical necessity when ALL of the following criteria are met:

1. Authorization/reauthorization has been previously approved by Florida Blue or another health plan in the past two years for treatment of breast cancer, OR the member has previously met all indication-specific criteria

2. Member has received less than one year of treatment with neratinib

3. Dose does not exceed 240 mg daily

Approval duration: 6 months

DOSAGE/ADMINISTRATION:

THIS INFORMATION IS PROVIDED FOR INFORMATIONAL PURPOSES ONLY AND SHOULD NOT BE USED AS A SOURCE FOR MAKING PRESCRIBING OR OTHER MEDICAL DETERMINATIONS. PROVIDERS SHOULD REFER TO THE MANUFACTURER’S FULL PRESCRIBING INFORMATION FOR DOSAGE GUIDELINES AND OTHER INFORMATION RELATED TO THIS MEDICATION BEFORE MAKING ANY CLINICAL DECISIONS REGARDING ITS USAGE.

FDA-approved

• Antidiarrheal prophylaxis: Initiate loperamide with the first dose o and continue during first 2 cycles (56 days) of treatment.

• Recommended dose: 240 mg (6 tablets) given orally once daily with food, continuously for one year.

• Dose interruptions and/or dose reductions are recommended based on individual safety and tolerability.

Dose Adjustments

• Hepatic Impairment: Reduce starting dose to 80 mg in patients with severe hepatic impairment

Drug Availability

• Tablets: 40 mg

PRECAUTIONS:

Boxed Warning

• None

Contraindications

• None

Precautions/Warnings

• Diarrhea

• Hepatotoxicity

• Embryo-Fetal Toxicity

BILLING/CODING INFORMATION:

The following codes may be used to describe:

HCPCS Coding

J8999

Prescription drug, oral, chemotherapeutic, Not Otherwise Specified

ICD-10 Diagnoses Codes That Support Medical Necessity

C50.011 – C50.929

Malignant neoplasm of breast

REIMBURSEMENT INFORMATION:

Refer to section entitled POSITION STATEMENT.

PROGRAM EXCEPTIONS:

Federal Employee Program (FEP): Follow FEP guidelines.

State Account Organization (SAO): Follow SAO guidelines.

Medicare Part D: BCBSF has delegated to Prime Therapeutics authority to make coverage determinations for the Medicare Part D services referenced in this guideline.

Medicare Advantage: No National Coverage Determination (NCD) and/or Local Coverage Determination (LCD) were found at the time of the last guideline review date.

DEFINITIONS:

Adjuvant Treatment: Additional cancer treatment given after the primary treatment to lower the risk that the cancer will return. Adjuvant therapy may include chemotherapy, radiation therapy, hormone therapy, targeted therapy, or biologic therapy. Adjuvant therapy can be used after or in combination with another form of cancer therapy and is commonly used following removal of a cancerous tumor to further help in treatment.

Metastatic cancer: when cancer spreads from the primary site (place where it started) to other places in the body.

Neo-adjuvant treatment: Treatment given as a first step to shrink a tumor before the main treatment, which is usually surgery, is given. Examples of neoadjuvant therapy include chemotherapy, radiation therapy, and hormone therapy. It is a type of induction therapy

RELATED GUIDELINES:

Carboplatin (Paraplatin®) IV, 09-J0000-93

Docetaxel (Taxotere®) IV, 09-J0000-95

Doxorubicin HCl Liposome (Doxil®) IV, 09-J0000-91

Gemcitabine (Gemzar®), 09-J0000-96

Irinotecan HCl Camptosar®) IV, 09-J0000-99

Oxaliplatin (Eloxatin®) IV, 09-J1000-00

Nab-Paclitaxel Injection (Abraxane)

Pertuzumab (Perjeta™) IV, 09-J1000-75

Trastuzumab (Herceptin®) Injection, 09-J0000-86

OTHER:

None applicable.

REFERENCES:

1. Chan A, Delaloge S, Holmes FA, et al. Neratinib after trastuzumab-based adjuvant therapy in patients with HER2-positive breast cancer (ExteNET): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2016 Mar;17(3):367-77.

2. Clinical Pharmacology [Internet]. Tampa (FL): Gold Standard, Inc.; 2015 [cited 7/27/17]. Available from: http://www.clinicalpharmacology.com/.

3. ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine; 2000 Feb 29 - [cited 7/27/17]. Available from: http://clinicaltrials.gov/.

4. DRUGDEX® System [Internet]. Greenwood Village (CO): Thomson Micromedex; Updated periodically [cited 7/27/17]. Available from: http://www.thomsonhc.com/.

5. National Comprehensive Cancer Network®. NCCN clinical practice guidelines in oncology (NCCN Guidelines®). Breast cancer, v. 2.2017 [cited 7/27/17]. Available from: http://www.nccn.org/professionals/physician_gls/f_guidelines.asp.

6. NCCN Drugs & Biologics Compendium [Internet]. Fort Washington (PA): National Comprehensive Cancer Network; 2015 [cited 7/27/17]. Available from: http://www.nccn.org/professionals/drug_compendium/content/contents.asp/.

7. Orphan Drug Designations and Approval [Internet]. Silver Spring (MD): US Food and Drug Administration; 2015 [cited ???]. Available from: http://www.accessdata.fda.gov/scripts/opdlisting/oopd/index.cfm/.

8. Puma. Nerlynx (neratinib) tablet. 2017 [cited 7/27/17]. In: DailyMed [Internet]. Bethesda (MD): National Library of Medicine. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/208051s000lbl.pdf.

COMMITTEE APPROVAL:

This Medical Coverage Guideline (MCG) was approved by the BCBSF Pharmacy Policy Committee on 08/09/17.

GUIDELINE UPDATE INFORMATION:

09/15/17

New Medical Coverage Guideline.

Date Printed: December 16, 2017: 09:27 PM